The Proteomics Core Facility at the University of Kentucky (UK) College of Medicine requests $947,163 to acquire a LTQ Orbitrap XL/ETD hybrid mass spectrometer with an Eksigent nano-HPLC. The goal of this application is to provide advanced mass spectrometry capabilities to meet the proteomics needs of 19 highly productive NIH-funded investigators at UK. The LTQ Orbitrap/ETD hybrid mass spectrometer is a combination of a new linear ion trap (LTQ), a novel and high precision electrostatic ion trap (Orbitrap) mass analyzer, and innovative electron transfer dissociation (ETD) technology. In comparison to the existing mass spectrometers for protein and peptide analysis, this hybrid instrument simultaneously provides high sensitivity (attomoles), high spectrum repetition rates, high mass resolution (60,000 HWFM), high mass accuracy (<5ppm), and complementary fragmentation techniques (both CID and ETD) during a single experiment. The instrumentation reaches a new level of sensitivity and confidence for identifying peptides and proteins. Moreover, the ETD technology provides multiple unique advantages. Particularly it can preserve the post-translation modifications on peptides during fragmentation and allow the identification of exact modification sites. This equipment will provide state-of-the-art capabilities to the Proteomics Core Facility and enhance the ability of the facility to meet an ever-increasing volume and intensity of research support. This equipment is essential to these ongoing research programs and to stimulating and enabling new collaborative research initiatives on protein identification, posttranslational modification characterization, gene discovery, and functional proteomics. Currently, there is no LTQ Orbitrap/ETD mass spectrometer at UK or any universities in the Commonwealth of Kentucky. The purchase of the instrument is critical to the continuing expansion and enhancement of the proteomics research program in human disease and basic research at UK. As described in this application, 19 NIH-funded investigators from 12 different departments have specific needs for this mass spectrometer. The requested instrument will have a major impact on research capabilities at our institution. To ensure the maximal usage and proper maintenance, the instrument will be housed in the Proteomics Core next to the laboratory of the PI. The PI has over 10 years experience in the area of biological mass spectrometry/proteomics. An Advisory Committee with both internal and external members is assembled for overall guidance for the usage of the shared instrument. Financial support for the long term maintenance and operation of the instrument is committed from the University. The research to be supported by this instrument spans a wide spectrum of biological and biomedical research, including cutting-edge programs focused on neurological disorders, cancer, diabetes, cardiovascular disease, virology, eye diseases, and women's health. The addition of this instrument to the Proteomics Core Facility at UK Medical Center will significantly enhance the productivity and progress of these research programs, thus advancing the NIH mission to improve public health. The funding of this proposal will lead to the hiring and/or retention of more than six full-time positions, including at least one in the University of Kentucky, four at Thermo Fisher Scientific, and one with Eksigent Technologies. Thus this proposal fits the criteria for Recovery Act funding. The manufacturers of the instrumentation (Thermo Fisher Scientific and Eksigent Technologies) are committed to being environmentally responsible. In particular, the splitless nano-HPLC manufactured by Eksigent Technologies uses significantly less organic solvents compared to other split-flow chromatography instruments, thus generating hundreds- to thousands-fold less chemical waste. Moreover, the biomedical research programs that will be enabled and supported by the requested instrumentation will make discoveries leading to better health of Americans. In summary, the funding of this application will make the United States and the world healthier, cleaner and safer. PUBLIC HEALTH RELEVANCE: The Proteomics Core Facility at the University of Kentucky (UK) College of Medicine requests $947,163 to acquire a LTQ Orbitrap XL ETD hybrid mass spectrometer with an Eksigent nano-HPLC. The goal of this application is to provide advanced mass spectrometry capabilities to meet the proteomics needs of 19 highly productive NIH-funded investigators at UK. The research to be supported by this instrument spans a wide spectrum of biological and biomedical research, including cutting-edge programs focused on neurological disorders, cancer, diabetes, cardiovascular disease, virology, eye diseases, and women's health. The addition of this instrument to the Proteomics Core Facility will significantly enhance the productivity and progress of these research programs, thus advancing the NIH mission to improve public health. The funding of this proposal will lead to the hiring and/or retention of more than six full-time positions, meeting the intention of the Recovery Act. The requested instruments are environmentally friendly. In summary, the funding of this application will make the United States and the world healthier, cleaner and safer.